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Trial record 12 of 3772 for:    colon cancer AND Intestinal Neoplasms

PK/PD Investigation of Modufolin® in Plasma, Tumor and Adjacent Mucosa Adjacent Mucosa in Patients With Colon Cancer

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ClinicalTrials.gov Identifier: NCT01681472
Recruitment Status : Completed
First Posted : September 10, 2012
Results First Posted : July 17, 2015
Last Update Posted : July 10, 2019
Sponsor:
Information provided by (Responsible Party):
Isofol Medical AB

Tracking Information
First Submitted Date  ICMJE September 5, 2012
First Posted Date  ICMJE September 10, 2012
Results First Submitted Date  ICMJE May 21, 2015
Results First Posted Date  ICMJE July 17, 2015
Last Update Posted Date July 10, 2019
Study Start Date  ICMJE September 2012
Actual Primary Completion Date August 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 1, 2019)
  • Concentration of [6R]-5,10-methylene-THF in Tumor Tissue [ Time Frame: Sample taken Day 1 (Day of surgery) at 0 min (before anesthetics) and 5, 10, 20, 40, 60, 90, 120, 180, 240, 360 min after study drug administration, and 24 h after study drug administration ]
    Comparison of concentration of the active substance in Modufolin: [6R]-5,10-methylene-THF in tumor tissue after the different treatments.
  • Concentration of [6R]-5,10-methylene-THF in Adjacent Mucosa Tissue [ Time Frame: Sample taken Day 1 (Day of surgery) at 0 min (before anesthetics) and 5, 10, 20, 40, 60, 90, 120, 180, 240, 360 min after study drug administration, and 24 h after study drug administration ]
    Comparison of concentration of the active substance in Modufolin: [6R]-5,10-methylene-THF in mucosa adjacent to the tumor after the different treatments.
  • Concentration of [6S]-5-THF in Tumor Tissue [ Time Frame: Sample taken Day 1 (Day of surgery) at 0 min (before anesthetics) and 5, 10, 20, 40, 60, 90, 120, 180, 240, 360 min after study drug administration, and 24 h after study drug administration ]
    Comparison of concentration of the metabolite [6S]-5-THF in tumor after the different treatments.
  • Concentration of [6S]-5-THF in Adjacent Mucosa Tissue [ Time Frame: Sample taken Day 1 (Day of surgery) at 0 min (before anesthetics) and 5, 10, 20, 40, 60, 90, 120, 180, 240, 360 min after study drug administration, and 24 h after study drug administration ]
    Comparison of concentration of the metabolite [6S]-5-THF in mucosa adjacent to the tumor after the different treatments.
  • Concentration of [6S]-5-methyl-THF in Tumor Tissue [ Time Frame: Sample taken Day 1 (Day of surgery) at 0 min (before anesthetics) and 5, 10, 20, 40, 60, 90, 120, 180, 240, 360 min after study drug administration, and 24 h after study drug administration ]
    Comparison of concentration of the metabolite [6S]-5-methyl-THF in tumor after the different treatments.
  • Concentration of [6S]-5-methyl-THF in Adjacent Mucosa Tissue [ Time Frame: Sample taken Day 1 (Day of surgery) at 0 min (before anesthetics) and 5, 10, 20, 40, 60, 90, 120, 180, 240, 360 min after study drug administration, and 24 h after study drug administration ]
    Comparison of concentration of the metabolite [6S]-5-methyl-THF in mucosa adjacent to the tumor after the different treatments.
  • Concentration of [6S]-5-formyl-THF in Tumor Tissue [ Time Frame: Sample taken Day 1 (Day of surgery) at 0 min (before anesthetics) and 5, 10, 20, 40, 60, 90, 120, 180, 240, 360 min after study drug administration, and 24 h after study drug administration ]
    Comparison of concentration of the metabolite [6S]-5-formyl-THF in tumor after the different treatments.
  • Concentration of [6S]-5-formyl-THF in Adjacent Mucosa Tissue [ Time Frame: Sample taken Day 1 (Day of surgery) at 0 min (before anesthetics) and 5, 10, 20, 40, 60, 90, 120, 180, 240, 360 min after study drug administration, and 24 h after study drug administration ]
    Comparison of concentration of the metabolite [6S]-5-formyl-THF in mucosa adjacent to the tumor after the different treatments.
Original Primary Outcome Measures  ICMJE
 (submitted: September 7, 2012)
Comparison of Folate Concentration in Tumor Tissue and Adjacent Mucosa Between Treatment Arms. [ Time Frame: Sample taken Day 1 (Day of surgery). ]
Change History Complete list of historical versions of study NCT01681472 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 26, 2019)
  • AUC(0-2h) of [6R]-5,10-methylene-THF [ Time Frame: Samples taken Day 1 (Day of surgery) ]
    Area under the plasma concentration versus time curve from time 0 to 2 hours, for the active substance in Modufolin: [6R]-5,10-methylene-THF
  • AUC(0-2h) of [6S]-5-THF [ Time Frame: Samples taken Day 1 (Day of surgery) ]
    Area under the plasma concentration versus time curve from time 0 to 2 hours, for the metabolite [6S]-5-THF
  • AUC(0-2h) of [6S]-5-methyl-THF [ Time Frame: Samples taken Day 1 (Day of surgery) ]
    Area under the plasma concentration versus time curve from time 0 to 2 hours, for the metabolite: [6S]-5-methyl-THF
  • AUC(0-2h) of [6SR]-5-formyl-THF [ Time Frame: Samples taken Day 1 (Day of surgery) ]
    Area under the plasma concentration versus time curve from time 0 to 2 hours, for the metabolite [6S]-5-formyl-THF
  • AUC(Last) of [6R]-5,10-methylene-THF [ Time Frame: Samples taken Day 1 (Day of surgery) and Day 2 ]
    Area under the plasma concentration versus time curve, from time 0 to the last time point, for the active substance in Modufolin: [6R]-5,10-methylene-THF
  • AUC(Last) of [6S]-5-THF [ Time Frame: Samples taken Day 1 (Day of surgery) and Day 2 ]
    Area under the plasma concentration versus time curve, from time 0 to the last time point, for the metabolite [6S]-5-THF
  • AUC(Last) of [6S]-5-methyl-THF [ Time Frame: Samples taken Day 1 (Day of surgery) and Day 2 ]
    Area under the plasma concentration versus time curve, from time 0 to the last time point, for the metabolite [6S]-5-methyl-THF
  • AUC(Last) of [6S]-5-formyl-THF [ Time Frame: Samples taken Day 1 (Day of surgery) and Day 2 ]
    Area under the plasma concentration versus time curve, from time 0 to the last time point, for the metabolite [6S]-5-formyl-THF
  • Cmax of [6R]-5,10-methylene-THF [ Time Frame: Samples taken Day 1 (Day of surgery) and Day 2 ]
    Maximum concentration (Cmax) in plasma of the active substance in Modufolin: [6R]-5,10-methylene-THF
  • Cmax of [6S]-5-THF in Plasma [ Time Frame: Samples taken Day 1 (Day of surgery) and Day 2 ]
    Maximum concentration (Cmax) in plasma of the metabolite [6S]-5-THF
  • Cmax of [6S]-5-methyl-THF in Plasma [ Time Frame: Samples taken Day 1 (Day of surgery) and Day 2 ]
    Maximum concentration (Cmax) in plasma of the metabolite [6S]-5-methyl-THF
  • Cmax of [6S]-5-formyl-THF in Plasma [ Time Frame: Samples taken Day 1 (Day of surgery) and Day 2 ]
    Maximum concentration (Cmax) in plasma of the active substance in Modufolin: [6R] 5,10- methylene-THF and the metabolites: [6S]-5-THF, [6S]-5-methyl-THF, and [6S]-5-formyl-THF
  • Tmax of [6R]-5,10-methylene-THF [ Time Frame: Samples taken Day 1 (Day of surgery) and Day 2 ]
    Timepoint (tmax) when Cmax in plasma occurs of the active substance in Modufolin: [6R]-5,10-methylene-THF
  • Tmax of [6S]-5-THF [ Time Frame: Samples taken Day 1 (Day of surgery) and Day 2 ]
    Timepoint (tmax) when Cmax in plasma occurs for the metabolite [6S]-5-THF
  • Tmax of [6S]-5-methyl-THF [ Time Frame: Samples taken Day 1 (Day of surgery) and Day 2 ]
    Timepoint (tmax) when Cmax in plasma occurs for the metabolite [6S]-5-methyl-THF
  • Tmax of [6S]-5-formyl-THF [ Time Frame: Samples taken Day 1 (Day of surgery) and Day 2 ]
    Timepoint (tmax) when Cmax in plasma occurs for the metabolite [6S]-5-formyl-THF
  • T(1/2) of [6R]-5,10-methylene-THF [ Time Frame: Samples taken Day 1 (Day of surgery) and Day 2 ]
    Terminal plasma elimination half-life time for the active substance in Modufolin: [6R]-5,10-methylene-THF
  • T(1/2) of [6S]-5-THF [ Time Frame: Samples taken Day 1 (Day of surgery) and Day 2 ]
    Terminal plasma elimination half-life time for the metabolite [6S]-5-THF
  • T(1/2) of [6S]-5-methyl-THF [ Time Frame: Samples taken Day 1 (Day of surgery) and Day 2 ]
    Terminal plasma elimination half-life time for the metabolite [6S]-5-methyl-THF
  • T(1/2) of [6S]-5-formyl-THF [ Time Frame: Samples taken Day 1 (Day of surgery) and Day 2 ]
    Terminal plasma elimination half-life time for the metabolite [6S]-5-formyl-THF
  • T(Last) of [6R]-5,10-methylene-THF [ Time Frame: Samples taken Day 1 (Day of surgery) and Day 2 ]
    The time-point for the last measurable concentration of the active substance in Modufolin: [6R]-5,10-methylene-THF
  • T(Last) of [6S]-5-THF [ Time Frame: Samples taken Day 1 (Day of surgery) and Day 2 ]
    The time-point for the last measurable concentration for the metabolite [6S]-5-TH in plasma
  • T(Last) of [6S]-5-methyl-THF [ Time Frame: Samples taken Day 1 (Day of surgery) and Day 2 ]
    The time-point for the last measurable concentration for the metabolite [6S]-5-methyl-THF in plasma
  • T(Last) of [6S]-5-formyl-THF [ Time Frame: Samples taken Day 1 (Day of surgery) and Day 2 ]
    The time-point for the last measurable concentration for the metabolite [6S]-5-formyl-THF in plasma
  • Correlation Between Plasma and Tissue Concentration (Tumor and Mucosa) for [6R]-5,10-methylene-THF [ Time Frame: Samples taken Day 1 (Day of surgery) ]
    Correlation between the exposure of [6R]-5,10-methylene-THF following 2 hours after dosing (AUC[0-2h]) and the concentration of [6R]-5,10-methylene-THF in the tumor or adjacent mucosa at surgery.
  • Correlation Between Plasma and Tissue Concentration (Tumor and Mucosa) for [6S]-5-THF [ Time Frame: Samples taken Day 1 (Day of surgery) ]
    Correlation between the exposure of [6S]-5-THF following 2 hours after dosing (AUC[0-2h]) and the concentration of [6S]-5-THF in the tumor or adjacent mucosa at surgery.
  • Correlation Between Plasma and Tissue Concentration (Tumor and Mucosa) for [6S]-5-methyl-THF [ Time Frame: Samples taken Day 1 (Day of surgery) ]
    Correlation between the exposure of [6S]-5-methyl-THF following 2 hours after dosing (AUC[0-2h]) and the concentration of [6S]-5-methyl-THF in the tumor or adjacent mucosa at surgery.
  • Correlation Between Plasma and Tissue Concentration (Tumor and Mucosa) for [6S]-5-formyl-THF [ Time Frame: Samples taken Day 1 (Day of surgery) ]
    Correlation between the exposure of [6S]-5-formyl-THF following 2 hours after dosing (AUC[0-2h]) and the concentration of [6S]-5-formyl-THF in the tumor or adjacent mucosa at surgery.
  • Gene Expression Ratios (Mucosa:Tumor) [ Time Frame: Sample taken Day 1 (Day of Surgery) ]
    Concentration of different genes involved in folate transport and metabolism were analysed in both tumor and adjacent mucosa. The concentration in mucosa was divided by the concentration in tumor. A value above 1 indicate that the gene expression was higher in mucosa than in tumor and a value below 1 that the gene expression was higher in tumor than in mucosa.
  • Correlation of Gene Expression in Tumor and Adjacent Mucosa [ Time Frame: Sample taken Day 1 (Day of Surgery) ]
    Concentration of the gene expression was analysed in both tumor and adjacent mucosa. The presence of any correlation between the results (i.e., concentration of the gene expression in tumor versus adjacent mucosa) was evaluated for each treatment. No evaluation was done between treatments.
  • Homocystein Concentration [ Time Frame: Samples taken at Screening visit, Day 2, and End of Study (Day 5) ]
    Blood samples for folate biomarker (homocystein) analysis were collected at Screening, Day 2, and Day 5 (End of study visit).
  • S-Folate Concentration [ Time Frame: Samples taken at Screening visit, Day 2 and End of Study (Day 5) ]
    Blood samples for folate biomarker (S-folate) analysis were collected at Screening, Day 2 and Day 5 (End of study visit).
  • Change in Homocystein Concentration From Screening [ Time Frame: Samples taken at Screening visit, Day 2 and End of Study (Day 5) ]
    Blood samples for folate biomarker (homocystein) analysis were collected at Screening, Day 2 and Day 5 (End of study visit). Changes from screening to later visits were counted. The criteria for assessment categories "normal", "low" and "high" were based on the reference ranges for plasma-Homocystein as follows: "low" <4,7 mcmol/L; "normal" => 4,7 and <=16 mcmol/L; "high" >16 mcmol/L. Values were applicable for both male and female adults.
  • Change in S-Folate Concentration From Screening [ Time Frame: Samples taken at Screening visit, Day 2 and End of Study (Day 5) ]
    Blood samples for folate biomarker (S-folate) analysis were collected at Screening, Day 2 and Day 5 (End of study visit). Changes from screening to later visits were counted.
  • Number of AEs Per Severity [ Time Frame: Screening visit until end of study, Day 5 ]
    Number of reported AEs per treatment with respect to severity
Original Secondary Outcome Measures  ICMJE
 (submitted: September 7, 2012)
  • To explore if there is a difference in pharmacokinetic parameters of [6R] 5,10- methylene-THF, 5-formyl-THF, 5-methyl-THF and THF calculated from plasma concentration [ Time Frame: Samples taken on Screening visit, Day 1 and Day 2. ]
  • To study safety in terms of adverse events and laboratory measurements; haematology, clinical chemistry and urinalysis. [ Time Frame: Screening visit until end of study, Day 5 ]
  • To study gene expression in tumor and mucosa. [ Time Frame: Sample taken Day 1 (Day of Surgery) ]
  • To study homocystein and serum folate levels. [ Time Frame: Samples taken at Screening visit, Day 2 and End of Study (Day 5) ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE PK/PD Investigation of Modufolin® in Plasma, Tumor and Adjacent Mucosa Adjacent Mucosa in Patients With Colon Cancer
Official Title  ICMJE A Single-Blind, Randomized Phase I/II Study of Pharmacokinetic and Pharmacodynamic Investigation of Modufolin® (60 or 200mg/m2) Compared to Levoleucovorin (60 or 200mg/m2) in Tumor, Adjacent Mucosa and Plasma for Patients With Colon Cancer
Brief Summary The purpose of this study is to compare the concentration of four different metabolites in the tumor, in adjacent mucosa and in plasma in patients with colon cancer receiving two different doses of Modufolin® and Levoleucovorin (Isovorin®), respectively (60 and 200 mg/m2).
Detailed Description The purpose of this study is to compare the concentration of [6R] 5,10-methylene-THF, 5-formyl-THF, 5-methyl-THF and THF in the tumor, in adjacent mucosa and in plasma in patients with colon cancer receiving two different does of Modufolin® and Levoleucovorin (Isovorin®), respectively (60 and 200 mg/m2).
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Investigator)
Primary Purpose: Treatment
Condition  ICMJE Colonic Neoplasms
Intervention  ICMJE
  • Drug: 6R-MTHF 200 mg/m2
    i.v. bolus injection
    Other Names:
    • Modufolin®
    • ISO-901
    • [6R] 5,10-methylenetetrahydrofolate
  • Drug: Levoleucovorin 200 mg/m2
    i.v. bolus injection
    Other Name: Isovorin®
  • Drug: 6R-MTHF 60 mg/m2
    i.v. bolus injection
    Other Names:
    • Modufolin®
    • ISO-901
    • [6R] 5,10-methylenetetrahydrofolate
  • Drug: Levoleucovorin 60 mg/m2
    i.v. bolus injection
    Other Name: Isovorin®
Study Arms  ICMJE
  • Active Comparator: Levoleucovorin 200 mg/m2
    One i.v. bolus injection of study drug after the patient has been anaesthetized.
    Intervention: Drug: Levoleucovorin 200 mg/m2
  • Active Comparator: Levoleucovorin 60 mg/m2
    One i.v. bolus injection of study drug after the patient has been anaesthetized.
    Intervention: Drug: Levoleucovorin 60 mg/m2
  • Experimental: 6R-MTHF 200 mg/m2
    One i.v. bolus injection of study drug after the patient has been anaesthetized.
    Intervention: Drug: 6R-MTHF 200 mg/m2
  • Experimental: 6R-MTHF 60 mg/m2
    One i.v. bolus injection of study drug after the patient has been anaesthetized.
    Intervention: Drug: 6R-MTHF 60 mg/m2
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 14, 2013)
32
Original Estimated Enrollment  ICMJE
 (submitted: September 7, 2012)
64
Actual Study Completion Date  ICMJE August 2013
Actual Primary Completion Date August 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Main Inclusion Criteria:

  • Operable colon cancer amenable to curative surgery.
  • Performance status of 0 to 1
  • Informed consent form
  • Patients must be at least 18 years of age.

Main Exclusion Criteria:

  • Any concurrent other anti-tumor therapy
  • Any prohibited concomitant medication within 30 days of surgery
  • Pregnancy or breast-feeding.
  • Second primary malignancy
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Sweden
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01681472
Other Study ID Numbers  ICMJE ISO-CC-002
2012-000522-22 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Isofol Medical AB
Study Sponsor  ICMJE Isofol Medical AB
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Kristoffer Derwinger, MD PhD Sahlgrenska University Hospital, Sweden
PRS Account Isofol Medical AB
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP